Hypothermia and hypometabolism: sensitive indices of whole-body toxicity following exposure to metallic salts in the mouse.
To investigate the practicality of hypothermia and hypometabolism as sensitive indices of toxicity in the mouse, oxygen consumption was monitored continuously and body temperature was measured at 30 min postinjection following the intraperitoneal administration of various metal salts. Eleven metal ions were tested: Al3+, Cd2+, Co2+, Cr2+, Cu2+, Hg2+, Mg2+, Mn2+, Ni2+, Pb2+, and Zn2+. All metals induced dose-dependent reductions in both oxygen consumption (hypometabolism) and deep body (colonic) temperature. Comparative toxicity of the metal ions was evaluated by calculating the dose of metal ion in dimensions of mmol/kg body mass needed to reduce colonic temperature to 35 degrees C. The order of toxicity from lowest to highest was as follows: Cr less than Al less than Pb less than Mn less than Mg less than Zn less than Cu less than Co less than Ni less than Hg less than Cd. The threshold doses for reducing body temperature were less than 5% of the LD50 in 6 of the metals studied. Metal salts with relatively low LD50 doses such as Hg, Cd, and Ni were most efficacious in inducing hypothermia and hypometabolism. Moreover, there was a direct linear relationship between dose for inducing hypothermia or hypometabolism and the reported LD50. Hence, the hypothermia and hypometabolism test may prove to be a sensitive and rapid test for the evaluation of toxicity of environmental contaminants.
Gordon
C J
CJ
Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Fogelson
L
L
Highfill
J W
JW
D000064:Acclimatization / Q000187:drug effects; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects; D007035:Hypothermia / Q000139:chemically induced*; D007928:Lethal Dose 50; D008660:Metabolism / Q000187:drug effects*; D008670:Metals / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D010101:Oxygen Consumption / Q000187:drug effects; D012044:Regression Analysis; D013997:Time Factors
D008670:Metals